Aerosilization of stem cells or stem cell derivatives for pulmonary delivery

Abstract

A treatment system delivers a breathing gas and frozen stem cells or other biologic particles (FBP) to a bronchus of a lung of a patient in order to treat lung and other conditions. The breathing gas and the FBP are usually delivered through separate lumens. The FBP may be delivered concurrently with other frozen particles, such as frozen saline particles (FSP). The FBP/FSP will remain frozen at all times from preparation to delivery, and will thaw only after they are released into the lung.

What is claimed is: 
     
       1. A method for delivering frozen biologic particles (FBP) to a bronchus of a lung of a patient, said method comprising:
 delivering a breathing gas stream to the bronchus of the lung of the patient; and 
 delivering FBP from an FBP source to the bronchus of the lung, wherein the FBP comprise a biologic material having an aqueous phase wherein the aqueous phase is frozen so that the material is formed into flowable particles having a size in the range from 4 μm to 100 μm, wherein the particles are capable of being carried into the lower lung of a patient by normal or induced respiration; 
 wherein the FBP are entrained in the breathing gas and carried by the breathing gas into the bronchus of the lung, wherein at least a portion of the aqueous phase of the FBP remains frozen as solid ice while being delivered to the bronchus of the lung and thaws only after the FBP are released into the lung. 
 
     
     
       2. A method as in  claim 1  wherein the FBP are frozen while in the FBP source and remain frozen while they are delivered and until they are released into the bronchus of the lung. 
     
     
       3. A method as in  claim 1  wherein the breathing gas and the FBP are delivered through separate lumens of a breathing tube. 
     
     
       4. A method as in  claim 1  wherein the breathing gas and the FBP are delivered through a common lumen in a breathing tube. 
     
     
       5. A method as in  claim 1  wherein the breathing gas and the FBP are delivered during at least a portion of some of the patient's inhalation cycles but not during the patient's exhalation cycles. 
     
     
       6. A method as in  claim 1  wherein delivering FBP to the bronchus of the lung comprises providing a bolus of FBP and flowing a volume of carrier gas through the bolus to entrain the FBP in the flowing carrier gas to produce an FBP-entrained flowing carrier gas stream which is delivered to the lung through a FBP lumen separate from the breathing gas. 
     
     
       7. A method as in  claim 6  further comprising venting a portion of the carrier gas from the FBP-entrained flowing carrier gas stream to produce a gas reduced FBP-entrained flowing carrier gas stream, wherein said gas reduced FBP-entrained flowing carrier gas stream is delivered to the FBP lumen. 
     
     
       8. A method for delivering frozen biologic particles (FBP) to a bronchus of a lung of a patient, said method comprising:
 dispersing a plurality of boluses of FBP into a flowing carrier gas to entrain the FBP in the flowing carrier gas to produce an FBP-entrained flowing carrier gas stream, wherein the FSB comprise a biologic material having an aqueous phase wherein the aqueous phase is frozen so that the material is formed into flowable particles having a size in the range from 4 m to 100 m, wherein the particles are capable of being carried into the lower lung of a patient by normal or induced respiration; 
 delivering the FBP-entrained flowing carrier gas stream to the bronchus of the lung of the patient simultaneously with a separate breathing gas stream in synchrony with the patient's inhalation cycle, wherein at least a portion of an aqueous content of the FBP remains frozen while being delivered having undergone a phase change from liquid water to solid ice. 
 
     
     
       9. A method as in  claim 8  wherein a single bolus is delivered with each inhalation, wherein an amount of FBP is controlled by adjusting the inhalation rate delivered by a ventilator. 
     
     
       10. A method as in  claim 8  wherein the amount of FBP delivered to the patient is controlled by adjusting an amount of FBP in individual boluses. 
     
     
       11. A method as in  claim 10  wherein a tidal volume of breathing gas delivered to the patient comprises a sum of a breathing gas volume and a carrier gas volume delivered on each inhalation cycle. 
     
     
       12. A method as in  claim 11  wherein the tidal volume of total breathing gas delivered to the patient is adjusted to a target level by venting a portion of the carrier gas from the FBP-entrained flowing carrier gas stream after dispersing the FBP therein and before delivering the FBP-entrained flowing carrier gas stream and separate breathing gas stream to the bronchus of the lung of the patient to produce a reduced FBP-entrained flowing carrier gas stream. 
     
     
       13. A method as in  claim 12  wherein the target level of tidal volume of total breathing gas is in the range from 150 ml to 1000 ml per inhalation cycle. 
     
     
       14. A method as in  claim 4  wherein a controller adjusts an amount or rate of delivery of the FBP from the FBP source through the at least one lumen of the breathing tube. 
     
     
       15. A method as in  claim 1  wherein the FBP source comprises an external source of frozen biological particles. 
     
     
       16. A method as in  claim 14  wherein the controller vents at least 50% of the gas originally present in the FBP-entrained flowing carrier gas stream to produce the gas reduced FBP-entrained flowing carrier gas stream. 
     
     
       17. A method as in  claim 1  wherein the biologic material comprises stem cells which remain viable after being released in the bronchus of the lung while still frozen and thereafter carried into the lower lung by normal or induced respiration. 
     
     
       18. A method as in  claim 1  further comprising delivering frozen saline particles (FSP) from an FSP source to the bronchus of the lung. 
     
     
       19. A method as in  claim 18  wherein the FSP are delivered concurrently with the FBP. 
     
     
       20. A method as in  claim 19  wherein the FSP are delivered in the same breathing gas stream as the FBP. 
     
     
       21. A method as in  claim 19  further comprising delivering a second breathing gas stream to the bronchus of the lung of the patient, wherein the FSP are entrained in the second breathing gas stream. 
     
     
       22. A method as in  claim 1  wherein the FBP are delivered through a thermally insulated lumen.